Yet Another Doctor Blog On The Internet

Treatment for the procoagulant state in type 2 diabetes.


In 1984 the General Practitioner Hypertension Study Group undertook a rescreening of their patient population, looking for patients who still had untreated mild to moderate essential hypertension. Suitable patients were entered into a clinical trial comparing the safety and efficacy of nicardipine (a calcium antagonist) and amiloride + hydrochlorothiazide (HCTZ) (moduretic). The study included one year of long-term follow-up. Both drugs significantly lowered BP in both the short and long term. Numbers and percentages of patients from each group reporting adverse experiences were similar in the short term, but in the long term the frequency of adverse event reporting was much lower with nicardipine treatment than with amiloride + HCTZ treatment (2/10 versus 9/17). Treatment with amiloride + HCTZ led to elevations in serum levels of cholesterol, uric acid and urea, which were maintained at one year, whilst no abnormalities in blood biochemistry were seen in patients treated with nicardipine. In conclusion we have found that nicardipine compares very favourably with amiloride + HCTZ in the treatment of mild to moderate hypertensive patients.

Acute effects of amiloride (5 mg) (A), hydrochlorthiazide (50 mg) (H) and the combination (50 + 5 mg) (HA) on urinary electrolyte excretion and pH of ten healthy volunteers--taking placebo five times and twice randomly A and HA and once H--were studied during one day. Amiloride showed a natriuretic effect, which in combination was additive to that of hydrochlorthiazide, but the excretion of water did not increase significantly after A. The urinary excretion of potassium decreased with amiloride below normal levels and was at the level of placebo after the combination (HA). There was a striking linear correlation between urinary sodium and potassium with all the drugs, although showing with A a higher potassium retention during high sodium excretion. Urinary pH rose after A and HA during the first 8 hours, but this effect was not seen, however, after H. No significant differences in the effect of the two brands of A (Medamor and Puritrid) on the urinary electrolyte excretion and pH, nor in those of the two brands of HA (Moduretic and Amitrid) were found. Similarly, the plasma concentrations of hydrochlorthiazide, determined gas chromatographically, were equal after Moduretic and Amitrid tablets. The systemic availability of H was faster in the combination of HA than alone. In the AUC value of H, however, there was no significant difference between HA and H tablets.

In a randomized double-blind study to compare the effect of atenolol vs. hydrochlorothiazide and amiloride (Moduretic) on left ventricular dimensions and systolic function, 100 hypertensive men were followed up during 1 year of treatment, 50 subjects being randomized to each drug. Echocardiography was performed at baseline, and after 3 and 12 months of treatment. A significant reduction in left ventricular mass with atenolol was paralleled by a decrease in left ventricular wall thickness and an increase in stroke volume. A similar reduction of left ventricular mass with Moduretic without a change in relative wall thickness and a decrease in stroke volume was observed. Cardiac output decreased in both groups.

This study, ancillary to the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), involved nifedipine 30 mg or co-amilozide (hydrochlorothiazide 25 mg and amiloride 2.5 mg) with optional subsequent titration. Among 439 randomized hypertensive patients, 324 had >/=1 year of follow-up (intent-to-treat group), and 242 completed follow-up (until-end-of-study group). Ultrasonography was performed at baseline, 4 months later, and then every year. Central computerized reading provided far-wall IMT, diameter, and cross-sectional area IMT (CSA-IMT). The primary outcome was IMT progression rate (slope of IMT-time regression). Secondary outcomes were changes from baseline (Delta) in IMT, diameter, and CSA-IMT. In the until-end-of-study population, between-treatment differences existed in IMT progression rate (P=0.002), Delta IMT (P=0.001), and Delta CSA-IMT (P=0.006), because IMT progressed on co-amilozide but not on nifedipine. In the intent-to-treat population, treatment differences existed in Delta IMT (P=0.004) and Delta CSA-IMT (P=0.04) but not in IMT progression rate (P=0.09). Patients with >/=2, 3, or 4 years of follow-up showed treatment differences in IMT progression rate (P=0.04, 0.004, 0.007, respectively), Delta IMT (P=0.005, 0.001, 0.005), and Delta CSA-IMT (P=0.025, 0.013, 0.015). Diameter decreased more on co-amilozide than on nifedipine in the intent-to-treat population (P<0.05), whereas blood pressure decreased similarly on both treatments.

Rapid, precise, accurate and specific ratio spectra derivative spectrophotometry and high-performance liquid chromatographic procedures were described for the simultaneous determination of hydrochlorothiazide and amiloride hydrochloride in combined pharmaceutical dosage forms. For the first method, ratio spectra derivative spectrophotometry, the signals were measured at 285.7 nm for hydrochlorothiazide and at 302.5 nm for amiloride hydrochloride in the mixture, in the first derivative of the ratio spectra. The second method is based on high-performance liquid chromatography (HPLC) on LiChrosorb RP-C18 column (5 microm, 20 cm x 4.6 mm) using 0.025 M orthophosphoric acid (adjusted to pH 3.0 with triethylamine (TEA)), acetonitrile (84:16 v/v) as a mobile phase at a flow rate of 1.2 ml/min(-1). Detection was carried out using a UV detector at 278.0 nm. Commercial sugar-coated and laboratory-prepared mixtures containing both drugs in different proportions were assayed using the developed methods.